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The human ZC3H3 and RBM26/27 proteins are critical for PAXT-mediated nuclear RNA decay.
Nucleic Acids Research ( IF 16.6 ) Pub Date : 2020-03-18 , DOI: 10.1093/nar/gkz1238
Toomas Silla 1 , Manfred Schmid 1 , Yuhui Dou 1 , William Garland 1 , Miha Milek 2, 3 , Koshi Imami 2, 4 , Dennis Johnsen 1 , Patrik Polak 1 , Jens S Andersen 5 , Matthias Selbach 2, 4 , Markus Landthaler 2, 3 , Torben Heick Jensen 1
Affiliation  

Recruitment of the human ribonucleolytic RNA exosome to nuclear polyadenylated (pA+) RNA is facilitated by the Poly(A) Tail eXosome Targeting (PAXT) connection. Besides its core dimer, formed by the exosome co-factor MTR4 and the ZFC3H1 protein, the PAXT connection remains poorly defined. By characterizing nuclear pA+-RNA bound proteomes as well as MTR4-ZFC3H1 containing complexes in conditions favoring PAXT assembly, we here uncover three additional proteins required for PAXT function: ZC3H3, RBM26 and RBM27 along with the known PAXT-associated protein, PABPN1. The zinc-finger protein ZC3H3 interacts directly with MTR4-ZFC3H1 and loss of any of the newly identified PAXT components results in the accumulation of PAXT substrates. Collectively, our results establish new factors involved in the turnover of nuclear pA+ RNA and suggest that these are limiting for PAXT activity.

中文翻译:

人ZC3H3和RBM26 / 27蛋白对于PAXT介导的核RNA衰变至关重要。

通过Poly(A)尾部脂质体靶向(PAXT)连接,可促进将人核糖核酸水解RNA外来物招募至核聚腺苷酸化(pA +)RNA。除了它的核心二聚体(由外来体辅助因子MTR4和ZFC3H1蛋白形成)之外,PAXT连接仍然定义不清。通过在有利于PAXT组装的条件下表征核pA + -RNA结合的蛋白质组以及包含MTR4-ZFC3H1的复合物,我们在这里发现了PAXT功能所需的三种其他蛋白质:ZC3H3,RBM26和RBM27以及已知的与PAXT相关的蛋白质PABPN1。锌指蛋白ZC3H3与MTR4-ZFC3H1直接相互作用,丢失任何新发现的PAXT组分会导致PAXT底物的积累。总的来说,
更新日期:2020-03-02
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